Recent advances in the treatment of HIV disease have produced dramatic reductions in AIDS-related morbidity) and mortality in the United States. In addition to effective drug combinations, clinicians now have available a range of laboratory techniques, including HIV RNA, resistance testing, and therapeutic drug monitoring. Yet these advances also give rise to new challenges in developing standards of patient care and allocating scarce resources. Over the past seven years, our research team has developed a computer simulation of HIV disease: the "Cost-effectiveness of Preventing AIDS Complications" or "CEPAC" model. We have used this model to address a host of important questions at the interface between HIV clinical care and HIV policy. In the first cycle of NlAlD support, we published 26 papers on topics ranging from the cost-effectiveness of antiretroviral therapy to the use of genotypic resistance testing.In this continuation, we propose to refine and update the CEPAC model to address emerging questions in HIV management and cost-effectiveness. We have four specific aims: (1) To assess the optimal timing of initiation of antiretroviral therapy for chronic HIV, considering the efficacy, long-term complications, cost, and cost-effectiveness of therapy; (2) To evaluate the clinical impact, cost, and cost-effectiveness of strategies using genotypic and/or phenotypic resistance testing as well as therapeutic drug monitoring combined with resistance testing; (3) To examine the clinical impact, long-term complications and cost-effectiveness of switching antiretroviral regimens based on both virologic (HIV RNA) and immunologic (CD4) parameters for patients at different stages of disease; and (4) To use the CEPAC model to conduct exploratory analyses of patient management decisions and to identify key variables in clinical areas where data are limited, including primary HIV infection and structured treatment interruption.We have a proven record of producing and disseminating findings that have helped to set priorities in HIV care, clinical trial design, and guideline development. Our aim, in the present proposal, is to exert an equally important impact in the years to come.